The human skin organ culture model as an optimal complementary tool for murine pemphigus models.

Hartmann, Veronika; Hariton, William VJ; Rahimi, Siavash; Hammers, Christoph M; Ludwig, Ralf J; Müller, Eliane J; Hundt, Jennifer E (2023). The human skin organ culture model as an optimal complementary tool for murine pemphigus models. Laboratory animals, 57(4), pp. 381-395. Sage 10.1177/00236772221145647

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Pemphigus is a severe autoimmune bullous disease of the skin and/or mucous membranes caused by autoantibodies that mainly target the adhesion proteins desmoglein (Dsg) 3 and/or Dsg1. Clinically, pemphigus is characterized by flaccid blistering, leading to severe water and electrolyte loss. Before the introduction of corticosteroid treatment, the disease turned out to be fatal in many cases. Despite recent therapeutic improvements, treatment of pemphigus patients is centred on prolonged systemic immunosuppression and remains challenging. Current drug development for pemphigus has a strong focus on disease-causing B cells and autoantibodies and, more recently, also on modulating autoantibody-induced tissue pathology and keratinocyte signalling. This drug development requires reliable pre-clinical model systems replicating the pathogenesis of the human disease. Among those are neonatal and adult mouse models based on the transfer of Dsg3, Dsg1/3 or Dsg1-specific autoantibodies. To reduce the number of animal experiments, we recently established a standardized human skin organ culture (HSOC) model for pemphigus. This model reproduces the clinical phenotype of autoantibody-induced tissue pathology in pemphigus vulgaris. For induction of blistering, a recombinant single-chain variable fragment (scFv) targeting both Dsg1 and 3 is injected into pieces of human skin (obtained from plastic surgeries). Further characterization of the HSOC model demonstrated that key morphologic, molecular and immunologic features of pemphigus are being replicated. Thus, the pemphigus HSOC model is an excellent alternative to pemphigus animal model systems that are based on the transfer of (auto)antibodies.

Item Type:

Journal Article (Review Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie > Forschungsgruppe Dermatologie

UniBE Contributor:

Hariton, William Vincent, Rahimi, Siavash, Müller, Eliane Jasmine

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1758-1117

Publisher:

Sage

Language:

English

Submitter:

Pubmed Import

Date Deposited:

23 Jan 2023 16:02

Last Modified:

07 Sep 2023 00:12

Publisher DOI:

10.1177/00236772221145647

PubMed ID:

36647613

Additional Information:

Veronika Hartmann, William VJ Hariton, Eliane J Müller and Jennifer E Hundt contributed equally.

Uncontrolled Keywords:

3R animal experimentation Desmoglein human skin organ culture in vitro model systems pemphigus

BORIS DOI:

10.48350/177594

URI:

https://boris.unibe.ch/id/eprint/177594

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